Clinical and Epidemiological Aspects of Multiple Sclerosis in Children.

Objective Overall, 2%-5% of patients with multiple sclerosis (MS) experienced the first episode of disease before the age 18 years old. Since the age of onset among children is not similar to that in general population, clinicians often fail to early diagnose the disease. This study aimed to determine the epidemiological and clinical patterns of MS among Iranian children. Materials & Methods In this cross-sectional study carried out in Iran in 2014-2015, information was collected using a checklist with approved reliability and validity. Method sampling was consensus. Data were analyzed using frequency, mean and standard deviation indices by means of SPSS ver. 20 software. Results Totally, 177 MS children were investigated. 75.7% of them were female. Mean (SD), minimum and maximum age of subjects were 15.9 (2), 7 and 18 yr, respectively. The most reported symptoms were sensory (28.2%), motor (29.4%), diplopia (20.3%) and visual (32.8%). Primary MRI results showed 91.5% and 53.1% periventricular and spinal cord lesions, respectively. Conclusion MS is significantly more common among women. The most common age of onset is during the second decades. Visual and motor problems are the most symptoms, while, periventricular and spinal cord lesions are the most MRI results.


Introduction
Multiple Sclerosis (MS) is one of the most common morbidities among young adults identifies with central nervous system demyelination (1,2). It was described pathologically for the first time in the 19th century (3). MS is associated with inflammation and degeneration of the myelin in CNS in the form of small and large single or multiple plaques and can lead to different complications such as reduced visual acuity, spastic paralysis and disability, sphincter disorders, impotence especially among men, imbalance, speech disorder, seizure, action tremor and depression (4,5). The main cause of MS is unknown and different etiologic factors have been reported. Various genetic, racial, environmental, infectious, toxic, immunologic and allergic by consensus method. After approving by Ethics Committee of Shahid Beheshti University of Medical Sciences, primary information of patients aged under 18 yr were collected from relevant clinical centers in Tehran (Sian Hospital, Mofid Hospital, Clinic of Dr. Sahraian, Clinic of Dr. Moghaddasi), Esfahan (Clinic of Dr Ashtari). Using a checklist including demographic and clinical variables such as age, gender, residence area, familial history, clinical manifestations at the onset and relapse, number of relapses, the time interval between the first attack and relapse and MRI results (initial and after three months). This checklist was designed based on previous similar studies (2)(3)(4)(14)(15)(16). Content validity was assessed according to the expert panels. To evaluate the reliability, objective items of the checklist (clinical characteristics) were completed for 10 patients and repeated after 10 d. The correlation between the answers was determined as of 0.79 using Spearman correlation. Descriptive statistics such as frequency, mean, standard deviation (SD) and median were estimated using SPSS software (Chicago, IL, USA).

Results
We recruited 177 MS children most of them were girl (75.7%). Mean±SD, minimum and maximum ages of them were 15.9±2, 7 and 18 yr, respectively. Of them, 35.6% were living in Tehran, 8.5% in Isfahan, 8.5% in Mazandaran and 32.7% in the other provinces. The residence area of the 26 (14.7%) were unknown. Moreover, 16.4% had familial history of MS (Table 1). The most common manifestations at the onset were impaired or loss of vision (32.8%), motor (29.4%) and sensory (28.2%) disorders. During the relapse, 31.6%, 30.5%, and 22.6% had sensory problems, motor problems and loss of vision, respectively ( Table 2). Among them, 17.5% reported more than three attacks. The time interval between the first attack and relapse was more than one year for 52.2% of patients (Table 3). Table 4 illustrates the MRI results.
factors were revealed (6)(7)(8)(9). Patients complain of a wide spectrum of signs and symptoms from mild to moderate and transient to persistent. Many of them show brain stem involvement such as vertigo, diplopia, cranial nerve paralysis, eye movement disorder, sensory, and motor symptoms as the first manifestations. It begins as local or sectional myelin degeneration in the central nervous system (CNS) among youth follows by irregular periods of cure and remission (2,3,5). Periodic neurologic attacks, disability and reduced physical, socio-economic and health quality during a 30-40 yr period of life is the main characteristics of MS (5). According to the disease trend and symptoms, it is characterized by relapsing-remitting type (70%), primary progressive and secondary progressive types (2,10,11). Prevalence of MS among women is four times of that among men (2). It normally occurs among young adults. Approximately, two-thirds of cases begin between ages 20-30 yr, most probably in 30-year-old age. However, it has been reported even among two-year-old children (2,3,8,12). According to a longitudinal study conducted in a Colombian hospital, 116 MS cases were identified before the age of 16 yr. Mean age of onset was 12.73 yr and the prevalence of early MS was 3.6% (13). Maximum and minimum ages of onset were 13 and 73 yr, respectively in Isfahan (14) and 4 and 13 yr, in Tehran (3). Since the age of onset among children is not in accordance with the common age of the disease, clinicians often fail to diagnose the disorder in the early stages. In addition, differential diagnosis of MS among children is of great importance and may be ignored during childhood leading to mental, psychological and economical problems for the families. Few relevant studies have been carried out. Different studies (2-3, 14-16) reported heterogenic results making it difficult to implement appropriate strategies. This study aimed to investigate comprehensively the epidemiological and clinical pattern of MS among Iranian children.

Materials & Methods
This cross-sectional study was conducted in 2015 among Iranian children suffering from MS selected

Discussion
Iranian women developed MS more than three folds greater than Iranian men did and mean age of the patients was approximately 16 yr. The most common signs and was symptoms during initial and relapse phases of disease were visual problems, ataxia and sensory-motor dysfunction. More than three attacks were observed among 17.5% of patients. More than half of them experienced some evidence of relapse at least one year after the first attack.  (3,8,12). During a longitudinal study carried out in a Colombian hospital, 116 incident cases were reported. The age of onset was before 16 for all cases with mean age of 12.73 yr 3.6% of them were early onset (17). Prevalence of early MS was reported as 19.8% in Jordan (10) and 3.6% in Russia (10). A retrospective study among 20 Iranian cases reported four and 13 yr as minimum and maximum age of onset (3). Since the age of onset among children is not in parallel with that among adults, clinicians often fail to early diagnose the pediatric MS. Two to five percent of cases experienced the first symptoms before 16 yr (18). The incidence of early MS before 16 has been reported as 0.4% to 10.5% globally (17). It can be an explanation for the observed disagreement between the age patterns and our results.

Author contribution
Nasehi MM, Sahraian MA, Ghofrani M and Moosazadeh M: Had substantial contributions to the conception and design of the work, analysis, interpretation of data and drafting the work and revising it critically for important intellectual content. Moghadasi AN, Ashtari F, Taghdiri MM, Tonekaboni SH, Karimzadeh P and Afshari M: Contributed to editing the manuscript, helping in gathering the data and final approval of the version to be published. All authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. positive familial history of MS, 40.5% of which were in the first-degree relatives (14). The above-mentioned results are in occurance with those found in our study. There were some limitations in the current study. We did not have access to the patients' information of all provinces in Iran, therefore, a geographical pattern was not provided by this study. The observed age of disease onset was not reliable but all cases have developed the disease before age 18. Finally, defects and high variations in patients' records made the research process slightly difficult. In conclusion, MS is considerably more common among women and starts commonly from the second decade of life. Moreover, sensory-motor manifestations, loss of muscle strength and level of consciousness were dominant signs and symptoms of the disease, while, periventricular and spinal cord lesions are the main MRI results during the MS development. To implement effective treatment strategies and strengthen the research foundations, it is necessary to design a comprehensive MS surveillance system within the community.